Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: UMLS:C0027947 (neutropenia)
17,527 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

This study examines the effectiveness of prophylactic ciprofloxacin and rifampin following high-dose chemotherapy and autologous stem cell rescue (HDC/ ASCR). Specific endpoints included the incidence of fever, clinically documented infection, bacteremia, and readmission rates from an outpatient bone marrow transplant setting following infection or fever. A group of 97 patients receiving 134 cycles of HDC/ASCR were studied. Patients were given ciprofloxacin 750 mg p.o. twice daily and rifampin 300 mg p.o. twice daily beginning on the day of stem cell reinfusion (24-48 h after completion of high-dose chemotherapy). Most patients were either discharged to an outpatient setting following completion of their chemotherapy or received all of their chemotherapy in an outpatient setting. Febrile neutropenia was treated with empirical antibiotics in an outpatient setting unless it was complicated by hypotension, renal failure, severe mucositis or other problems. The median duration of neutropenia (absolute neutrophil count below 500/mm3) was 7 days. Neutropenic fever occurred in 62% of patients but clinically documented bacterial infection occurred in only 2 (1.5%) patients during their neutropenic period. No bacteremia was noted. Readmission to the hospital following fever or infection occurred in 26% of patients maintained in the outpatient setting. There were no deaths from a bacterial infection in this study although 1 patient (0.7%) died from aspergillosis. Prophylactic ciprofloxacin and rifampin is a well-tolerated and highly effective combination that effectively decreases the risk of both gram-positive and gram-negative bacterial infection following HDC/ASCR. It facilitates outpatient management of myelosuppressed patients receiving autologous stem cell rescue.
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PMID:Prophylactic antibiotics eliminate bacteremia and allow safe outpatient management following high-dose chemotherapy and autologous stem cell rescue. 888 30

The pharmacokinetics and effects of recombinant human granulocyte colony-stimulating factor (rhG-CSF) on neutrophils and immunological function were studied in 10 patients with end-stage renal failure. A single dose and 2-week consecutive dosing of 50 micrograms/m2 of rhG-CSF were drip infused intravenously, and plasma rhG-CSF levels, peripheral blood cell counts, coagulation, and neutrophil and immunological functions were determined during treatment. The mean half-life of rhG-CSF in patients (2.47 +/- 0.64 h) was prolonged to about twice that of healthy subjects, and hemodialysis did not affect the pharmacokinetics. A marked increase in neutrophils and a slight increase in lymphocytes were observed with the single and consecutive administration of rhG-CSF, but no significant changes were noted in other leukocyte fractions and erythrocyte and platelet counts. The neutrophil alkaline phosphatase value increased significantly following rhG-CSF administration, and other neutrophil functions were also ameliorated in several patients with neutrophil dysfunction. In consecutive administration, however, mild bone pain and increased serum alkaline phosphatase were observed in about half the patients, but neither accumulation of rhG-CSF nor antibody production was detected. From these results, it is concluded that rhG-CSF is safe and effective for the treatment of neutropenia and neutrophil dysfunction in patients with renal failure.
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PMID:The effects and pharmacokinetics of rhG-CSF in patients with chronic renal failure. 896 84

Of 4,289 episodes of bacteremia detected in 3,631 patients, septic shock was diagnosed in 453 episodes (10.5%). In 56% of shock episodes, septic shock developed more than 24 h after the first positive blood culture was taken. In a logistic regression analysis, variables predictive of septic shock were: advanced age [odds ratio (OR) of 1.015 for an increment of 1 year]; renal failure as an underlying disorder (OR = 1.47); neutropenia (OR of 2.26); curtailed functional capacity (OR of 1.54 for an increment of 1 category); unknown source of infection (OR = 1.66); anaerobic (OR = 2.86), polymicrobial bacteremia (OR = 1.54), or pathogens other than Streptococcus viridans (OR = 0.08 for Streptococcus viridans). The in-hospital mortality associated with septic shock was 80% vs 21% in episodes of bacteremia without shock, and shock episodes accounted for 31% of all deaths. The fatality rate in shock patients given appropriate empiric antibiotic treatment was 74.9% vs 84.7% in patients given inappropriate treatment (p = 0.01). Judging by the present results, host factors are more important determinants for development of septic shock in bacteremic patients than the type of pathogen. Even in patients with shock, appropriate empiric antibiotic treatment was associated with an improved chance of survival.
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PMID:Septic shock in bacteremic patients: risk factors, features and prognosis. 911 2

The increasing doses of 2.4-3.5 g/m2 ifosfamide, i/v, dropwise, were administered for 40 min, on days 1-5 each week, for 3 weeks, in 4 courses. Simultaneously, MESNA was given in a dose two-thirds of that of ifosfamide. The maximum single tolerable dose of ifosfamide was 3.2 g/m2. The dose of 3.5 g/m2 proved neurotoxic causing encephalopathy. The other toxic effects were stage III-IV neutropenia (47%), nausea and vomiting (91%) and weakness (33%). No clinical evidence of renal failure was attributed to the high dosage of the drug in the course of assays of biochemical components of the blood, blood- and urine-beta-2-microglobulins, N-acetyl-D-hexoaminidase (NAG) level in urine, creatinine clearance and complex renoscintigraphy data. On days 3-5, ifosfamide treatment was followed by increase in NAG and beta-2-microglobulin levels in urine which pointed to the toxic effect exerted on the epithelium of renal tubules. The antitumor effect was apparent in 5 (29%) patients for 6 months, which testifies to the high effectiveness of ifosfamide treatment for soft-tissue sarcoma.
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PMID:[High-dose ifosfamide in the treatment of patients with soft tissue sarcoma]. 912 96

High-dose ifosfamide (HD-IFX) has shown significant antitumor activity in advanced sarcoma and breast carcinoma. The use of uroprotective agents and the availability of ambulatory continuous-infusion pumps has allowed dose escalation in the administration of ifosfamide (IFX) on an outpatient schedule. We report the results of a phase II trial of IFX given at high doses to heavily pretreated patients. IFX was infused at 2 g/m2 per day for a total of 7 days through a central venous access, with cycles being repeated every 21 days. Mesna was given concomitantly at equimolar doses. No hematopoietic support was used. A total of 27 heavily pretreated patients whose disease had progressed during conventional-dose chemotherapy were included (14 sarcomas, 10 breast carcinomas, and 3 bladder carcinomas). Reversible neutropenia and gastrointestinal toxicity were the most frequently encountered toxicities. Only two patients developed transient renal failure, and two others developed central nervous system toxicity. No treatment-related death was observed. Of 22 patients who were evaluable for response, 6 (27%) showed an objective response (OR), all ORs being partial responses (PRs) with a median duration of 6 months, and 12 patients had stable disease (SD; 55%) with a median duration of 3.5 months. The median overall survival (OS) was 6 months. Three patients underwent high-dose chemotherapy after showing a response to our IFX schedule. We conclude that continuous-infusion IFX given in an outpatient setting is a feasible and active regimen that produces, a manageable toxicity profile in heavily pretreated breast cancer and sarcoma patients. Early institution of this schedule in less advanced stages could improve the results obtained.
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PMID:Feasibility trial of high-dose 7-day continuous-infusion ifosfamide given on an outpatient basis. 921 13

The function of neutrophil can be evaluated by measuring oxidative metabolism using chemiluminescence, tetrazolium dye reduction or the others. Those results are not always satisfactory which would be caused by subtle difference in each preparation of the reagents and the lack of reproducibility. Recently, flow cytometric procedures for semi-quantitating superoxide production in neutrophils have been developed to evaluate their function. This procedure, which requires only small amount of whole blood, can easily and rapidly yield reproducible and reliable data. In this study, we optimized analytical conditions and then determined reference interval to evaluate neutrophil function of patients with various disorders. Optimal concentrations and incubation times of DCFH-DA and PMA were 5 mumol/l for 15 minutes and 25 micrograms/ml for 20 minutes, respectively. Production of superoxide in neutrophil was represented by relative fluorescence intensity(RFI) with assay coefficient of variance(CV) of 4.0-11.1%. Neutrophils had to be examined within 2 hours after venipuncture to obtain reliable data. Reference interval was determined as 170.4 +/- 58.7(mean +/- SD) RFI. Neutrophil function of patients with neutropenia, paroxysmal nocturnal hemoglobinuria(PNH), renal failure, systemic lupus erythematosus(SLE), myeloperoxidase deficiency, myelodysplastic syndrome(MDS), and diabetes mellitus were within the reference interval as evaluated by this method. Only neutrophils of chronic granulomatous disease, which is known to give clearly low superoxide production, showed actually decreased value. These results indicate that this procedure would be clinically useful for diagnosis of patient with impaired neutrophil function.
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PMID:[Determination of neutrophil function by measuring superoxide production with whole blood flow cytometry]. 939 45

Fifty-one transfusion-dependent iron-loaded adult patients (38 with thalassemia major) were treated with the orally active iron chelator deferiprone (1,2 dimethyl-3-hydroxypyrid-4-one, L1) at a dose of 75 mg/kg/d (range, 50 to 79). Twenty patients discontinued the drug and five died after a mean of 18.7 months (range, 4 to 35). Of the 20, 5 had arthropathy, 5 had gastrointestinal symptoms, 4 had a rising serum ferritin, 3 had agranulocytosis or neutropenia, 1 had tachycardia, 1 had renal failure, and 1 went abroad. Twenty-six patients continued deferiprone for a mean of 39.4 months (range, 12 to 49). Among these patients, there was no overall significant change in serum ferritin (initial mean, 2,937 microg/L; range, 980 to 5,970; final mean, 2,323 microg/L; range, 825 to 5,970) or in urine iron excretion (initial mean, 31.2 mg/24 h; range, 16.3 to 58. 2; final mean, 32.1 mg/24 h; range, 9.4 to 75.8), implying no overall change in iron stores. When the patients who had received deferiprone for longer than 3 years were considered separately, there was also no significant change in serum ferritin or urinary iron excretion. The initial serum ferritin levels in the 26 patients who continued deferiprone treatment were significantly lower than in those who discontinued the drug (P < .01). The liver iron content in 17 patients who had received deferiprone for 24 to 48 months ranged from 5.9 to 41.2 mg/g dry weight, 50% having levels above 15.0 mg, a level associated with a high risk of cardiac disease due to iron overload. In this study the drug caused fewer side effects and was more effective at maintaining iron status among patients previously well chelated and with lower initial serum ferritin levels.
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PMID:Long-term trial of deferiprone in 51 transfusion-dependent iron overloaded patients. 941 97

Many patients with solid tumours or haematological malignancies develop anaemia, and the use of chemotherapy aggravates this condition. Red blood cell transfusions are often necessary but are associated with many risks, including immunosuppressive effects that may increase the risk of tumour recurrence. Many clinical studies have shown that epoetin (recombinant human erythropoietin) therapy can ameliorate, or even prevent, the anaemia associated with chemotherapy and cancer (including solid tumours as well as multiple myeloma or lymphoma). Response, defined as a significant (>50%) reduction in the rate of transfusions and/or a significant (>2 g/dl) elevation of haemoglobin levels, is usually observed in about 60% of the patients, irrespective of the type of standard chemotherapy given. The decrease in transfusion requirements is the major objective of epoetin therapy, because they are costly, inconvenient and are associated with potential adverse effects. Epoetin therapy also brings about substantial improvements in various indices of quality of life that are proportional to changes in haemoglobin level. However, large dosages of epoetin are generally required and about 40% of patients do not respond even to very high dosages. A number of adverse effects of epoetin therapy have been observed in patients with renal failure. The most prominent include hypertension, headaches, seizures and thrombotic events. These complications can also occur in patients with renal failure who are not receiving epoetin. Their exact incidence has been assessed in placebo-controlled studies, which have demonstrated that there is no increased risk of thrombosis or seizure with epoetin. However, it is now generally accepted that 10 to 20% of haemodialysis patients will experience an elevation of blood pressure because of epoetin and there is no doubt that a rapid elevation of blood pressure may cause generalised seizures. In other settings, including anaemia associated with cancer, very few adverse effects have been attributed to epoetin. However, close monitoring of blood pressure should be implemented in patients with hypertension. There is no evidence that epoetin stimulates tumour growth. With the dosages of epoetin currently used, there is no evidence of stem cell competition, resulting in thrombocytopenia or neutropenia, or of stem cell exhaustion, producing secondary anaemia when treatment is stopped. Epoetin is a remarkably well tolerated drug that offers significant benefits in patients with cancer.
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PMID:A risk-benefit assessment of epoetin in the management of anaemia associated with cancer. 980 42

Ecteinascidin 743 (ET-743) is a cytotoxic tetrahydroisoquinoline alkaloid that covalently binds to DNA in the minor groove. The in vitro chemosensitivity of cancer cells to ET-743 is markedly enhanced by prolonging the duration of exposure to the drug. A Phase I study of ET-743 given as a 72-h continuous i.v. infusion every 21 days was performed. Characteristics of the 21 adult patients with refractory solid tumors enrolled in the study were as follows: (a) 12 men; (b) 9 women; (c) median age, 59 years; (d) Eastern Cooperative Oncology Group performance status < or = 1, 20 patients; and (e) two prior regimens of chemotherapy, 7 patients. Dose limiting toxicity (DLT) was defined by typical criteria, except that grade 3 transaminitis did not constitute a DLT. There were no DLTs in the six patients evaluated at the first two dose levels of 600 and 900 microg/m2. Reversible grade 4 transaminitis occurred in two of nine patients after treatment with the first cycle of therapy at the third dose level of 1200 microg/m2. Another patient experienced grade 4 rhabdomyolysis, renal failure requiring hemodialysis, grade 4 neutropenia, and grade 3 thrombocytopenia during the second cycle of therapy with this dose. The maximum tolerated dose was 1200 microg/m2, and an additional six patients were enrolled at an intermediate dose level of 1050 microg/m2. This well-tolerated dose was established as the recommended Phase II dose. The disposition of ET-743 was distinctly biexponential, and a departure from linear pharmacokinetic behavior was evident at the 1200-microg/m2 dose level. Pharmacokinetic parameters determined at 1050 microg/m2 were (mean +/- SD): maximum plasma concentration, 318 +/- 147 pg/ml; initial disposition phase half-life, 9.0 +/- 10.3 min; terminal phase half-life, 69.0 +/- 56.7 h; and total plasma clearance, 28.4 +/- 22.5 liters/h/m2. Prolonged systemic exposure to concentrations of the agent that are cytotoxic in vitro were achieved. Toxicity of the drug is clearly schedule-dependent, because increasing the duration of infusion from 3 or 24 h to 72 h results in decreased myelosuppression and comparable hepatotoxicity. Although there were no objective responses to therapy, clear evidence of antitumor activity was observed in a patient with epithelioid mesothelioma, as confirmed by positron emission tomography studies. A Phase II trial to assess the efficacy of ET-743 against this highly refractory neoplasm has been initiated on the basis of this observation. The therapeutically optimal administration schedule remains to be established, inasmuch as there have been indications of activity against a variety of tumors during Phase I studies when the drug was infused over times ranging from 1 to 72 h. Characterizing the pharmacokinetics of ET-743 during the course of Phase II trials and Phase I combination studies is recommended to assure that this promising new anticancer drug can be used with an acceptable margin of safety.
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PMID:Phase I and pharmacokinetic study of ecteinascidin 743 administered as a 72-hour continuous intravenous infusion in patients with solid malignancies. 1123 74

Acquired pure red cell aplasia (PRCA) can be associated with lymphoproliferative disease of granular T lymphocytes (T-LDGL), also known as T-cell large granular lymphocyte leukemia. Fifteen adult patients with PRCA associated with T-LDGL comprise this study. Neutropenia and rheumatoid arthritis were uncommon. All patients responded to immunosuppressive therapy. The 2 most commonly used treatments were prednisone and cyclophosphamide +/- corticosteroids, producing overall response rates of 50% and 60%, respectively. Treatment with cyclophosphamide was associated with a more durable remission (median, 60 versus 7.5 months). After a median follow-up of 67 months, 2 patients died of treatment-related complications, one from myelodysplasia and another from cyclosporine-induced renal failure. The clinical course and treatment responses of PRCA associated with T-LDGL in this series were similar to the general group of PRCA. Because T-LDGL is frequently underdiagnosed, it is likely that a significant proportion of idiopathic or primary PRCA is in fact secondary to T-LDGL.
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PMID:Acquired pure red cell aplasia associated with lymphoproliferative disease of granular T lymphocytes. 1143 21


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